Factor VIII/von Willebrand Factor (FVIII/vWF) is a large glycoprotein with which FVIII procoagulant and vWF activities are associated. The separation of the FVIII procoagulant activity from the vWF activity by a variety of methods has led to a considerable controversy about the molecular structure of factor VIII. To help resolve this controversy, FVIII/vWF will be purified to homogeneity. The proteins associated with the two activities will be separated by chromatography or sucrose gradient ultracentrifugation in high ionic strength buffers and characterized by a variety of biochemical and immunological techniques. Since some of our recent experiments strongly suggest that modification by thrombin may be necessary for the generation of FVIII procoagulant activity, the FVIII procoagulant and vSF activity will be modified by such agents as dithiothreitol and ethylenediamine tetraacetate. FVIII/vWF will be fragmented by enzymatic or cyanogen bromide cleavage and the fragments analyzed for the two activities and antigenicity. The reaction of thrombin with factor VIII will be studied in considerable detail.